4.8 Article

The gut metabolite 3-hydroxyphenylacetic acid rejuvenates spermatogenic dysfunction in aged mice through GPX4-mediated ferroptosis

期刊

MICROBIOME
卷 11, 期 1, 页码 -

出版社

BMC
DOI: 10.1186/s40168-023-01659-y

关键词

Aging; Spermatogenic dysfunction; Gut microbiota; 3-Hydroxyphenylacetic acid; Ferroptosis

向作者/读者索取更多资源

Our study explored the mechanism of how the microbiota affects male reproductive aging by utilizing fecal microbiota transplantation (FMT) and identified a gut bacteria-derived metabolite, 3-HPAA, that facilitates spermatogenesis in old mice through a ferroptosis-mediated mechanism. These findings provide a novel understanding of dysregulated spermatogenesis in aging males and suggest that 3-HPAA could be a potential therapy for fertility decline in clinical practice.
BackgroundAging-related fertility decline is a prevalent concern globally. Male reproductive system aging is mainly characterized by a decrease in sperm quality and fertility. While it is known that intestinal physiology changes with age and that microbiota is shaped by physiology, the underlying mechanism of how the microbiota affects male reproductive aging is still largely unexplored.ResultsHere, we utilized fecal microbiota transplantation (FMT) to exchange the fecal microbiota between young and old mice. Cecal shotgun metagenomics and metabolomics were used to identify differences in gut microbiota composition and metabolic regulation during aging. Our results demonstrated that FMT from young to old mice alleviated aging-associated spermatogenic dysfunction through an unexpected mechanism mediated by a gut bacteria-derived metabolite, 3-hydroxyphenylacetic acid (3-HPAA). 3-HPAA treatment resulted in an improvement of spermatogenesis in old mice. RNA sequencing analysis, qRT-PCR and Western blot revealed that 3-HPAA induced an upregulation of GPX4, thereby restraining ferroptosis and restoring spermatogenesis. These findings were further confirmed by in vitro induction of ferroptosis and inhibition of GPX4 expression.ConclusionsOur results demonstrate that the microbiome-derived metabolite, 3-HPAA, facilitates spermatogenesis of old mice through a ferroptosis-mediated mechanism. Overall, these findings provide a novel mechanism of dysregulated spermatogenesis of old mice, and suggest that 3-HPAA could be a potential therapy for fertility decline of aging males in clinical practice.5pcYmaM61yMj7bgSVcSwU1Video AbstractConclusionsOur results demonstrate that the microbiome-derived metabolite, 3-HPAA, facilitates spermatogenesis of old mice through a ferroptosis-mediated mechanism. Overall, these findings provide a novel mechanism of dysregulated spermatogenesis of old mice, and suggest that 3-HPAA could be a potential therapy for fertility decline of aging males in clinical practice.5pcYmaM61yMj7bgSVcSwU1Video Abstract

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据